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The initial discovery of key developmental signalling pathways, largely using classical genetic approaches in model organisms, was followed by an intense burst of characterisation of the molecular components. Studies also began demonstrating a role for these pathways in oncogenesis. Patterns of mutations in Notch pathway components, such as those reported in sub-sets of hematological malignancies, have been easier to study, and the cumulative information is leading to potentially new therapies. However, it has been more challenging to clearly define the role of the Notch pathway in human solid tumours, given the absence of widespread specific activating or repressive mutations in key components of the pathway. In this review, we trace more than two decades of work looking at the role of Notch signalling in human cervical cancer progression. We document the contrasting reports on a tumour suppressive role and pro-oncogenic role in cervical cancers. However, an analysis of recent genomic data strikingly shows both widespread features of Notch expression and genetic changes that largely amplify positive regulators and delete negative controllers of the Notch pathway. This analysis reinforces a largely pro-oncogenic role for Notch signalling and lays the foundation for a nuanced exploration of synergistic and targeted therapies. Lastly, we further trace some of the complex challenges in advanced cervical cancer progression, including issues of cancer stem cells and metastasis.
This article was published in the following journal.
Name: Experimental cell research
Persistent human papillomavirus (HPV) infection is the leading cause of cervical cancer. Although the fundamental link between HPV infection and oncogenesis is established, the specific mechanisms of ...
The most frequent cancers among women worldwide. The mortality of cervical cancer has declined significantly primarily due to the widespread use of Pap smear tests as a screening test and therapeutic ...
Cervical cancer is the second most common gynecologic cancer affecting the lives of women. It causes hundreds of thousands of death among women annually worldwide. When a woman is screened for cervica...
Uterine cervical cancer is the fourth most common female cancer in the world. In Japan, we have an apparently low rate of joining cervical cancer screening programs compared with Western countries. Fu...
Cervical cancer has been one of the most common cancer in women worldwide. However, the detailed mechanism underlying circMTO1-regulated cervical cancer remains unclear.
An investigational study to determine the safety/tolerability, and efficacy of a notch signaling pathway inhibitor in patients with metastatic or locally advanced breast cancer and other a...
This randomized phase I/II clinical trial is studying the side effects and best dose of gamma-secretase/notch signalling pathway inhibitor RO4929097 when given together with vismodegib and...
A Notch signalling pathway inhibitor study in pediatric and adult patients with relapsed (worsening) or refractory (not responding to treatment) T-cell acute lymphoblastic leukemia/lymphom...
This phase Ib/II trial studies the side effects and best dose of gamma-secretase/Notch signalling pathway inhibitor RO4929097 when given together with cisplatin, vinblastine, and temozolom...
This phase II clinical trial is studying how well RO4929097 works in treating patients with recurrent or progressive glioblastoma. RO4929097 may stop the growth of tumor cells by blocking ...
Morphological abnormalities of the cervical EPITHELIUM, usually revealed in PAP SMEAR, which do not meet the criteria for squamous CERVICAL INTRAEPITHELIAL NEOPLASIA or SQUAMOUS CELL CARCINOMAS of the CERVIX . It may be a sign of infection with certain types of human papillomavirus (HPV).or sign of a benign (not cancer) growth, such as a cyst or polyp or, in menopausal women, of low hormone levels. More testing, such as HPV test, may be needed.
A network of nerve fibers originating in the upper four cervical spinal cord segments. The cervical plexus distributes cutaneous nerves to parts of the neck, shoulders, and back of the head, and motor fibers to muscles of the cervical spinal column, infrahyoid muscles, and the diaphragm.
A parameter usually used in PRENATAL ULTRASONOGRAPHY to measure the length of the uterine neck (CERVIX UTERI). Cervical length or its shortening is used to identify and prevent early cervical opening and PRETERM BIRTH.
A notch receptor that plays an important role in CELL DIFFERENTIATION in a variety of cell types. It is the preferentially expressed notch receptor in mature B-LYMPHOCYTES.
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
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